The structure of 4′-demethylepipodophyllotoxin is shown in Formula (I), it can be extracted from podophyllin plants such as Sinopoclophyllum hexandrum, Diphylleia sinensis, Disporum leschenaultianum and so on.

Because of its strong toxic side effects and poor bioavailability, the natural lead compound with specific anti-tumor activity is confined in its clinic applications. Therefore, the drug development research on its structural modification is very active currently.
By introducing aryl groups in the 4-position of C ring of podophyllotoxin with β-carbon nitrogen bond, the derivatives obtained generally show good inhibitive activity on the tumor cells (Bioorgan Med Chem 2005; 13(22):6218-6225); a 4-amino-substituted derivative on the C ring in 4′-demethylepipodophyllotoxin is currently undergoing Phase II clinical trials (Anticancer Res, 2006, 26 (3A): 2149-2156); a US patent: U.S. Ser. No. 07/987,765 recorded a C ring 4-aminated derivative developed as an anti-tumor drug. Up to now, in the above-mentioned reports on the structure modifications and drug developments, the introduction of pyrazinyl group in 4-position on C ring has been unseen.
Ligustrazine (tetramethylpyrazine) is the active component of the traditional Chinese medicine Chuanxiong (Umbelliferae plant Szechuan Lovage Rhizome, Ligusticum chuanxiong Hort.), its structure is shown in (II),

Tetramethylpyrazine attains its anti-tumor efficacy by means of its effects of direct inhibition on the tumors, synergizing chemotherapy as well as immunomodulation; tetramethylpyrazine also mitigates the drug resistance of tumor cells, it also plays a role in antagonizing the metastasis of tumor cells by impacting tumor adherence and -invasion, as well as by means of its effects of anticoagulation and anti-platelet aggregation.